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This work reports the first catalytic N-methylation of primary amides using CO2. BICAAC plays a dual role in activating the amide and CO2 during catalysis.

Herein we report the first metal-free regioselective Markovnikov ring-opening of epoxides (selectivity up to 99%) using an abnormal N-heterocyclic carbene (aNHC) to yield secondary alcohols. DFT calculations and X-ray crystallography suggest that the Markovnikov selectivity originates from the high nucleophilicity and steric factors associated with the aNHC.

In recent years, the applications of low-valent main group compounds have gained momentum in the field of catalysis. Owing to the accessibility of two lone pairs of electrons, NHC-stabilised phosphinidenes have been found to be excellent Lewis bases; however, they cannot yet be used as catalysts. Herein, an NHC-stabilised phosphinidene, 1,3-dimethyl-2-(phenylphosphanylidene)-2,3-dihydro-1H imidazole (1), for the activation of CO2 is reported.A closer inspection of the CO2 activation process by DFT calculations along with intrinsic bond orbital analysis shows that phosphinidene is associated with phenylsilane through a noncovalent π-π interaction between two phenyl rings which activates the Si-H bond facilitating hydride transfer to the CO2 molecule. Detailed DFT studies along with spectroscopic experiments were combined to understand the mechanism of CO2 activation and its catalytic reductive functionalisation leading to the formylation of a range of chemically inert primary amides under mild reaction conditions.

Boron neutron capture therapy (BNCT) remains an important treatment arm for cancer patients with locally invasive malignant tumors. This therapy needs a significant amount of boron to deposit in cancer tissues selectively, sparing other healthy organs. Most of the liposomes contain water-soluble polyhedral boron salts stay in the core of the liposomes and have low encapsulation efficiency. Thus, modifying the polyhedral boron core to make it hydrophobic and incorporating those into the lipid layer could be one of the ways to increase drug loading and encapsulation efficiency. Additionally, a systematic study about the linker-dependent effect on drug encapsulation and drug-release is lacking, particularly for the liposomal formulation of hydrophobic-drugs. To achieve these goals, liposomal formulations of a series of lipid functionalized cobalt bis(dicarbollide) compounds have been prepared, with the linkers of different hydrophobicity. Hydrophobicity of the linkers have been evaluated through logP calculation and its effect on drug encapsulation and release have been investigated. The liposomes have shown high drug loading, excellent encapsulation efficiency, stability, and non-toxic behavior. Release experiment showed minimal release of drug from liposomes in phosphate buffer, ensuring some amount of drug, associated with liposomes, can be available to tumor tissues for Boron Neutron Capture Therapy.

Significant efforts have been made to develop new platinum anticancer compounds since the discovery of cis-platin; however, non-specific toxicity or loss of efficacy remain some of the major challenges in this area of platinum drug discovery. Newly developed platinum compounds, structurally distinct from the current molecules, imparting efficacy at lower concentrations than the current drugs, and interacting with DNA leading to cell death, may prove beneficial. In the current study, we designed, synthesized, and characterized three phenalenyl based platinum chloride compounds (1, 2, and 3) with the goal that a labile Pt–Cl bond with the planar structure of the phenalenyl moiety would enhance their interaction with DNA, leading to improved efficacy. In addition, it is assumed that the fluorescent properties of these compounds would facilitate mechanistic investigation. The crystal structure of compound 1 demonstrates a perfectly planar structure with a single Pt–Cl bond. In vitro cell viability studies on cancer cell lines, including lung, colorectal, breast, and osteosarcoma, revealed a superior efficacy for compounds 1 and 2, relative to platinum drugs in clinical use. Localization studies utilized the strong fluorescence of compound 3 to investigate the mechanism of action, revealing its interaction with DNA, leading to cell death. This study enriches the arsenal of potential platinum-based anti-cancer therapeutics and provides an easy-to-use tool for the mechanism-of-action studies of these compounds.

An abnormal N-heterocyclic carbene (aNHC) based potassium complex was used as a transition metal-free catalyst for reduction of primary amides to corresponding primary amines under ambient conditions. Only 2 mol% loading of the catalyst exhibits a broad substrate scope including aromatic, aliphatic and heterocyclic primary amides with excellent functional group tolerance. This method was applicable for reduction of chiral amides and utilized for the synthesis of pharmaceutically valuable precursors on a gram scale. During mechanistic investigation, several intermediates were isolated and characterized through spectroscopic techniques and one of the catalytic intermediates was characterized through single-crystal XRD. A well-defined catalyst and isolable intermediate along with several stoichiometric experiments, in situ NMR experiments and the DFT study helped us to sketch the mechanistic pathway for this reduction process unravelling the dual role of the catalyst involving nucleophilic activation by aNHC along with Lewis acidic activation by K ions., An abnormal N-heterocyclic carbene (aNHC) based potassium complex was used as a transition metal-free catalyst for reduction of primary amides to corresponding primary amines under ambient conditions.

Bicyclic (alkyl)(amino)carbene (BICAAC) is introduced as a metal-free catalyst for the reduction of various nitriles to the corresponding amine hydrochloride salts in the presence of pinacolborane. Mechanistic investigations combining experiments and DFT calculations suggest a B-H addition to the carbene center, which acts as a carrier of the hydride source.

Over exploitation of natural resources and human activities are relentlessly fueling the emission of CO2 in the atmosphere. Accordingly, continuous efforts are required to find solutions to address the issue of excessive CO2 emission and its potential effects on climate change. It is imperative that the world looks towards a portfolio of carbon mitigation solutions, rather than a single strategy. In this regard, the use of CO2 as a C1 source is an attractive strategy as CO2 has the potential to be a great asset for the industrial sector and consumers across the globe. In particular, the reduction of CO2 offers an alternative to fossil fuels for various organic industrial feedstocks and fuels. Consequently, efficient and scalable approaches for the reduction of CO2 to products such as methane and methanol can generate value from its emissions. Accordingly, in recent years, metal-free catalysis has emerged as a sustainable approach because of the mild reaction conditions by which CO2 can be reduced to various value-added products. The metal-free catalytic reduction of CO2 offers the development of chemical processes with low cost, earth-abundant, non-toxic reagents, and low carbon-footprint. Thus, this perspective aims to present the developments in both the reduction and reductive functionalization chemistry of CO2 during the last decade using various metal-free catalysts., This review article documents the key developments in the metal-free catalytic reduction of CO2 into various energy intensive chemicals and fuels, and reductive functionalization of CO2 for the formation of new C–N bonds.

In recent years, merging different types of catalysis in a single pot has drawn considerable attention and these catalytic processes have mainly relied upon metals. However, development of a completely metal free approach integrating organic redox and organic Lewis acidic property into a single system has been missing in the current literature. This study establishes that a redox active phenalenyl cation can activate one of the substrates by single electron transfer process while the same can activate the other substrate by a donor-acceptor type interaction using its Lewis acidity. This approach has successfully achieved light and metal-free catalytic C-H functionalization of unactivated arenes at ambient temperature (39 entries, including core moiety of a top-selling molecule boscalid), an economically attractive alternative to the rare metal-based multicatalysts process. A tandem approach involving trapping of reaction intermediates, spectroscopy along with density functional theory calculations unravels the dual role of phenalenyl cation.

Herein we report the hydroheteroarylation of vinylarenes with benzoxazole in the presence of a free abnormal N-heterocyclic carbene and Ni(COD)2, resulting in 1,1-diarylethane products exclusively. In an attempt to understand the mechanism of this catalytic reaction, two abnormal-NHC (aNHC)-coordinated Ni(II) cyclooctenyl complexes were isolated and their solid-state structures were determined by X-ray crystallographic studies. These Ni(II) cyclooctenyl complexes act as active catalyst precursors to generate in situ aNHC-Ni(0) species, which undergo oxidative addition with heteroarene to form Ni(II) hydride intermediates.

Herein, we report a versatile catalytic system for the direct C–H arylation of heteroarenes with activated aryl chloride substrates. The catalyst works successfully for a variety of heteroarenes and aryl chloride coupling partners under very low catalyst-loading conditions. We have successfully performed the direct C–H arylations of 1-methylpyrrole, 1-methylindole, furan, thiophene, furfural, and N-benzyl-1,2,3-triazole with aryl chloride partners in good yields without the use of any additives. Furthermore, we used this catalytic process to develop a one-pot synthetic protocol for the muscle relaxant dantrolene on a gram scale. Additionally, the present catalytic system can be used to perform consecutive arylations in one pot.

The radical-mediated transition metal-free approach for the direct C–H bond functionalization of arenes is considered as a cost effective alternative to transition metal-based catalysis. An organic ligand-based radical plays a key role by generating an aryl radical which undergoes a subsequent functionalization process. The design principle of the present study takes advantage of a relatively stable odd alternant hydrocarbon-based phenalenyl (PLY) radical. In this study, the first transition metal-free catalyzed direct C–H arylation of a variety of heteroarenes such as azoles, furan, thiophene and pyridine at room temperature has been reported using a phenalenyl-based radical without employing any photoactivation step. This protocol has been successfully applied to the gram scale synthesis of core moieties of bioactive molecules. The phenalenyl-based radical initiator has been characterized crystallographically by trapping it via the formation of a C–C σ-bond between the phenalenyl radical and solvent-based radical species.

NHCN-heterocyclic carbenenNHCnormal N-heterocyclic carbeneaNHCabnormal N-heterocyclic carbenePLY9-hydroxy-1H-phenalenoneIMes1,3‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylideneIAd1,3-bis(1-adamentyl) imidazol-2-ylideneSIMes1,3‐bis(2,4,6‐trimethylphenyl)imidazolin‐2‐ylideneIPr1,3-bis(diisopropylphenyl)imidazolylideneItBu1,3-bis(tert-butyl)imidazol-2-ylideneIMes·HClN,N′-bis-mesityl-imidazolium chlorideSIPrN,N-bis(2,6-diisopropyl)phenyl-substituted NHCeVelectron voltArarylmgmilligram/milligramsDMSOdimethyl sulfoxideTHFtetrahydrofuranACNAcetonitrileCD3CNacetonitrile‑d3DMFdimethylformamideToltolueneEtOHethanolMeOHmethanolHClhydrochloric acidDCMdichloromethaneOEt2diethyletherTMEDAtetramethylethylenediamineDCEdichloroethaneC6H6benzeneMTBEmethyl tert-butyl etherMesmesityl/2,4,6-trimethylphenylKOtBupotassium tert-butoxideNaOtBusodium tert-butoxideNaBHEt3sodium triethylborohydrideOTftriflateClchlorideBrbromideEtMgBrethyl magnesium bromideNaOHsodium hydroxideet al.and others (Latin alii)NEt3triethylamineKpotassiumZnzincCOD1,5-cyclooctadieneCOcarbonylCpcyclopentadienylν(CO)stretching frequency (cm−1)KHMDSpotassium hexamethyldisilazide [KN(SiMe3)2]Dipp2,6-diisopropyl-phenylnBuLin-butyllithiumLDALithium diisopropylamideHzhertzhhour/hoursddayequiv.equivalent/equivalentsoCdegree celsiusNMRnuclear magnetic resonanceδchemical shift1H NMRproton nuclear magnetic resonance13C NMRcarbon-13 nuclear magnetic resonance29Si NMRsilicon-29 nuclear magnetic resonanceppmparts per millionSiMe3trimethylsilylBnbenzyltButert-butyliPrisopropylEtethylMemethylAdadamentylCNcyanideUVultra-violetrtroom temperaturePhSiH3phenylsilanePh2SiH2diphenylsilanePh3SiHtriphenylsilanePhMe2SiHdimethyphenylsilaneEt3SiHtriethylsilane(OEt)2SiH2diethoxysilane(OEt)3SiHtriethoxysilanePhSiH2OHphenylsilanolPMHSpolymethylhydrosiloxaneTMDS1,1,3,3-tetramethyldisiloxaneTONturnover numberTOFturnover frequencyDRAdirect reductive aminationPDIpyridine(diimine)NDInaphthyridine-diiminedppb1,4-bis(diphenylphosphino)butaneDPEphosbis[(2-diphenylphosphino)phenyl] etherXantphos4,5-bis(diphenylphosphino)-9,9-dimethylxantheneMn2(CO)10dimanganese decacarbonylFe(OAc)2iron (II) acetateFe(acac)3iron (III) acetylacetonateFe3(CO)12triiron dodecacarbonylCo(OAc)2cobalt (II) acetateCoCl2cobalt (II) chlorideCo(OPiv)2cobalt (II) pivalateCo2(CO)8dicobalt octacarbonylNi(OAc)2nickel (II) acetateNi(acac)2nickel acetylacetonate (II)Cu(OTf)2copper (II) triflateInCl3indium trichloride

This work describes the dehydrogenative coupling of heteroarenes using a dimeric halo-bridged palladium(II) catalyst bearing an abnormal NHC ( aNHC) backbone. The catalyst can successfully activate the C-H bond of a wide range of heteroarenes, which include benzothiazole, benzoxazole, thiophene, furan, and N-methylbenzimidazole. Further, it exhibited good activity for heteroarenes bearing various functional groups such as CN, CHO, Me, OMe, OAc, and Cl. Additionally, we isolated the active catalyst by performing stoichiometric reaction and characterized it as the acetato-bridged dimer of ( aNHC)PdOAc by single-crystal X-ray study.